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bioRxiv · 10.1101/2024.05.07.593069

Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes

Pudjihartono, M. A.·Pudjihartono, N. M.·O'Sullivan, J. M.·Schierding, W.
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Abstract

Investigations of the non-coding region are essential for uncovering the full spectrum of genetic drivers in melanoma. Here, we map distal, non-coding, promoter-interacting regulatory elements using Hi-C data from melanoma cells and integrating these with whole-genome sequence and gene expression data from the Pan Cancer Analysis of Whole Genomes. We identified eight recurrently mutated hotspots that are melanoma-specific, alter transcription factor binding motifs, and affect the expression of genes (e.g. HSPB7, CLDN1, ADCY9 and FDXR) previously implicated as tumor suppressors/oncogenes. Our study integrates multiple levels of biological data to uncover novel melanoma-specific non-coding candidate drivers beyond the well-characterized TERT promoter.

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Pudjihartono, M. A., Pudjihartono, N. M., O'Sullivan, J. M., Schierding, W.. 2024-05-10. Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes. https://doi.org/10.1101/2024.05.07.593069

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